2-[6-Chloro-3-[(3,5-dimethylphenyl)methyl]-2,4-dioxo-pyrimidin-1-yl]acetonitrile | 890524-76-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[6-Chloro-3-[(3,5-dimethylphenyl)methyl]-2,4-dioxo-pyrimidin-1-yl]acetonitrile
• 英文别名: 2-[6-chloro-3-[(3,5-dimethylphenyl)methyl]-2,4-dioxopyrimidin-1-yl]acetonitrile
• CAS: 890524-76-2
• 化学式: C₁₅H₁₄ClN₃O₂
• 分子量: 303.748
• InChiKey: AFANZENRRMZYEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  64.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[6-Chloro-3-[(3,5-dimethylphenyl)methyl]-2,4-dioxo-pyrimidin-1-yl]acetonitrile 在 吡啶 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.5h， 生成 {3-(3,5-Dimethyl-benzyl)-2,4-dioxo-6-[4-(toluene-4-sulfonyl)-piperazin-1-yl]-3,4-dihydro-2H-pyrimidin-1-yl}-acetonitrile
  参考文献：
  名称：

  1-取代的3-（3,5-二甲基苄基）尿嘧啶衍生物的合成及其抗HIV-1和抗HCMV活性。

  摘要：

  在碱存在下用烷基卤处理3-（3,5-二甲基苄基）尿嘧啶（3），得到1-取代的同类物。使用Mitsunobu反应将3与醇缩合也用作替代方法。根据先前建立的程序评估3-（3,5-二甲基苄基）尿嘧啶的1-取代类似物的抗HIV-1活性。看来1-氰甲基的氮对于抗HIV-1活性是重要的，表明与HIV-1逆转录酶的氨基酸残基相互作用。1-芳基甲基衍生物也显示出良好的抗HIV-1活性。并且2-和4-吡啶甲基衍生物的特别好。这些结果已通过Docking Studies使用“ Glide配体对接工作”程序进行了确认，

  DOI：

  10.1248/cpb.54.325
• 作为产物：
  描述：

  1-methoxymethyl-6-chlorouracil 在 偶氮二甲酰胺 、 B-溴代邻苯二氧硼烷 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 2-[6-Chloro-3-[(3,5-dimethylphenyl)methyl]-2,4-dioxo-pyrimidin-1-yl]acetonitrile
  参考文献：
  名称：

  Synthesis and evaluation of novel 3-(3,5-dimethylbenzyl)uracil analogs as potential anti-HIV-1 agents

  摘要：

  A novel series of uracil derivatives with a 3,5-dimethylbenzyl group at the N-3-position were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. Some of these compounds showed good-to-moderate activity with EC50 values in the submicromolar range. Among them, compound 10c showed significant potency against HIV-1 activity with an EC50 value of 0.03 mu M and a high selectivity index of 2863. Preliminary structure-activity relationships and molecular modeling analyses were used to explore the major interactions between HIV-1 reverse transcriptase and the potent inhibitor 10c, which may serve as an important lead for further optimization. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.061

文献信息

• Synthesis and Anti-HIV-1 and Anti-HCMV Activity of 1-Substituted 3-(3,5-Dimethylbenzyl)uracil Derivatives
  作者：Tokumi Maruyama、Shigetada Kozai、Yosuke Demizu、Myriam Witvrouw、Christophe Pannecouque、Jan Balzarini、Robert Snoecks、Graciella Andrei、Erik De Clercq

  DOI：10.1248/cpb.54.325

  日期：——

  3-(3,5-Dimethylbenzyl)uracil (3) was treated with alkyl halides in the presence of alkali to give 1-substituted congeners. Condensation of 3 with alcohols using the Mitsunobu reaction was also employed as an alternative method. The anti-HIV-1 activity of 1-substituted analogues of 3-(3,5-dimethylbenzyl)uracil was evaluated according to previously established procedures. It appeared that the nitrogen

  在碱存在下用烷基卤处理3-（3,5-二甲基苄基）尿嘧啶（3），得到1-取代的同类物。使用Mitsunobu反应将3与醇缩合也用作替代方法。根据先前建立的程序评估3-（3,5-二甲基苄基）尿嘧啶的1-取代类似物的抗HIV-1活性。看来1-氰甲基的氮对于抗HIV-1活性是重要的，表明与HIV-1逆转录酶的氨基酸残基相互作用。1-芳基甲基衍生物也显示出良好的抗HIV-1活性。并且2-和4-吡啶甲基衍生物的特别好。这些结果已通过Docking Studies使用“ Glide配体对接工作”程序进行了确认，
• Synthesis and evaluation of novel 3-(3,5-dimethylbenzyl)uracil analogs as potential anti-HIV-1 agents
  作者：Norikazu Sakakibara、Takayuki Hamasaki、Masanori Baba、Yosuke Demizu、Masaaki Kurihara、Kohji Irie、Masatoshi Iwai、Eriko Asada、Yoshihisa Kato、Tokumi Maruyama

  DOI：10.1016/j.bmc.2013.06.061

  日期：2013.9

  A novel series of uracil derivatives with a 3,5-dimethylbenzyl group at the N-3-position were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. Some of these compounds showed good-to-moderate activity with EC50 values in the submicromolar range. Among them, compound 10c showed significant potency against HIV-1 activity with an EC50 value of 0.03 mu M and a high selectivity index of 2863. Preliminary structure-activity relationships and molecular modeling analyses were used to explore the major interactions between HIV-1 reverse transcriptase and the potent inhibitor 10c, which may serve as an important lead for further optimization. (C) 2013 Elsevier Ltd. All rights reserved.